Risk factors for non-atopic asthma/wheeze in children and adolescents: a systematic review

Background: The study of non-atopic asthma/wheeze in children separately from atopic asthma is relatively recent. Studies have focused on single risk factors and had inconsistent findings. Objective: To review evidence on factors associated with non-atopic asthma/wheeze in children and adolescents. Methods: A review of studies of risk factors for non-atopic asthma/wheeze which had a non-asthmatic comparison group, and assessed atopy by skin-prick test or allergen-specific IgE. Results: Studies of non-atopic asthma/wheeze used a wide diversity of definitions of asthma/wheeze, comparison groups and methods to assess atopy. Among 30 risk factors evaluated in the 43 studies only 3 (family history of asthma/rhinitis/eczema, dampness/mold in the household, and lower respiratory tract infections in childhood) showed consistent associations with non-atopic asthma/wheeze. No or limited period of breastfeeding was less consistently associated with non-atopic asthma/wheeze. The few studies examining the effects of overweight/obesity and psychological/social factors showed consistent associations. We used a novel graphical presentation of different risk factors for non-atopic asthma/wheeze, allowing a more complete perception of the complex pattern of effects. Conclusions: More research using standardized methodology is needed on the causes of non-atopic asthma.